Module hierarchy and centralisation in the anatomy and dynamics of human cortex

Systems neuroscience has recently unveiled numerous fundamental features of the macroscopic architecture of the human brain, the connectome, and we are beginning to understand how characteristics of brain dynamics emerge from the underlying anatomical connectivity. The current work utilises complex network analysis on a high-resolution structural connectivity of the human cortex to identify generic organisation principles, such as centralised, modular and hierarchical properties, as well as specific areas that are pivotal in shaping cortical dynamics and function. After confirming its small-world and modular architecture, we characterise the cortex’ multilevel modular hierarchy, which appears to be reasonably centralised towards the brain’s strong global structural core. The potential functional importance of the core and hub regions is assessed by various complex network metrics, such as integration measures, network vulnerability and motif spectrum analysis. Dynamics facilitated by the large-scale cortical topology is explored by simulating coupled oscillators on the anatomical connectivity. The results indicate that cortical connectivity appears to favour high dynamical complexity over high synchronizability. Taking the ability to entrain other brain regions as a proxy for the threat posed by a potential epileptic focus in a given region, we also show that epileptic foci in topologically more central areas should pose a higher epileptic threat than foci in more peripheral areas. To assess the influence of macroscopic brain anatomy in shaping global resting state dynamics on slower time scales, we compare empirically obtained functional connectivity data with data from simulating dynamics on the structural connectivity. Despite considerable micro-scale variability between the two functional connectivities, our simulations are able to approximate the profile of the empirical functional connectivity. Our results outline the combined characteristics a hierarchically modular and reasonably centralised macroscopic architecture of the human cerebral cortex, which, through these topological attributes, appears to facilitate highly complex dynamics and fundamentally shape brain function

Greater lifestyle engagement is associated with better age-adjusted cognitive abilities.

Previous evidence suggests that modifiable lifestyle factors, such as engagement in leisure activities, might slow the age-related decline of cognitive functions. Less is known, however, about which aspects of lifestyle might be particularly beneficial to healthy cognitive ageing, and whether they are associated with distinct cognitive domains (e.g. fluid and crystallized abilities) differentially. We investigated these questions in the cross-sectional Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data (N = 708, age 18-88), using data-driven exploratory structural equation modelling, confirmatory factor analyses, and age-residualized measures of cognitive differences across the lifespan. Specifically, we assessed the relative associations of the following five lifestyle factors on age-related differences of fluid and crystallized age-adjusted abilities: education/SES, physical health, mental health, social engagement, and intellectual engagement. We found that higher education, better physical and mental health, more social engagement and a greater degree of intellectual engagement were each individually correlated with better fluid and crystallized cognitive age-adjusted abilities. A joint path model of all lifestyle factors on crystallized and fluid abilities, which allowed a simultaneous assessment of the lifestyle domains, showed that physical health, social and intellectual engagement and education/SES explained unique, complementary variance, but mental health did not make significant contributions above and beyond the other four lifestyle factors and age. The total variance explained for fluid abilities was 14% and 16% for crystallized abilities. Our results are compatible with the hypothesis that intellectually and physically challenging as well as socially engaging activities are associated with better crystallized and fluid performance across the lifespan

Activity and Connectivity Differences Underlying Inhibitory Control Across the Adult Life Span.

Inhibitory control requires precise regulation of activity and connectivity within multiple brain networks. Previous studies have typically evaluated age-related changes in regional activity or changes in interregional interactions. Instead, we test the hypothesis that activity and connectivity make distinct, complementary contributions to performance across the life span and the maintenance of successful inhibitory control systems. A representative sample of healthy human adults in a large, population-based life span cohort performed an integrated Stop-Signal (SS)/No-Go task during functional magnetic resonance imaging (n = 119; age range, 18-88 years). Individual differences in inhibitory control were measured in terms of the SS reaction time (SSRT), using the blocked integration method. Linear models and independent components analysis revealed that individual differences in SSRT correlated with both activity and connectivity in a distributed inhibition network, comprising prefrontal, premotor, and motor regions. Importantly, this pattern was moderated by age, such that the association between inhibitory control and connectivity, but not activity, differed with age. Multivariate statistics and out-of-sample validation tests of multifactorial functional organization identified differential roles of activity and connectivity in determining an individual's SSRT across the life span. We propose that age-related differences in adaptive cognitive control are best characterized by the joint consideration of multifocal activity and connectivity within distributed brain networks. These insights may facilitate the development of new strategies to support cognitive ability in old age.SIGNIFICANCE STATEMENT The preservation of cognitive and motor control is crucial for maintaining well being across the life span. We show that such control is determined by both activity and connectivity within distributed brain networks. In a large, population-based cohort, we used a novel whole-brain multivariate approach to estimate the functional components of inhibitory control, in terms of their activity and connectivity. Both activity and connectivity in the inhibition network changed with age. But only the association between performance and connectivity, not activity, differed with age. The results suggest that adaptive control is best characterized by the joint consideration of multifocal activity and connectivity. These insights may facilitate the development of new strategies to maintain cognitive ability across the life span in health and disease

Influence of wiring cost on the large-scale architecture of human cortical connectivity

In the past two decades some fundamental properties of cortical connectivity have been discovered: small-world structure, pronounced hierarchical and modular organisation, and strong core and rich-club structures. A common assumption when interpreting results of this kind is that the observed structural properties are present to enable the brain's function. However, the brain is also embedded into the limited space of the skull and its wiring has associated developmental and metabolic costs. These basic physical and economic aspects place separate, often conflicting, constraints on the brain's connectivity, which must be characterized in order to understand the true relationship between brain structure and function. To address this challenge, here we ask which, and to what extent, aspects of the structural organisation of the brain are conserved if we preserve specific spatial and topological properties of the brain but otherwise randomise its connectivity. We perform a comparative analysis of a connectivity map of the cortical connectome both on high- and low-resolutions utilising three different types of surrogate networks: spatially unconstrained (‘random’), connection length preserving (‘spatial’), and connection length optimised (‘reduced’) surrogates. We find that unconstrained randomisation markedly diminishes all investigated architectural properties of cortical connectivity. By contrast, spatial and reduced surrogates largely preserve most properties and, interestingly, often more so in the reduced surrogates. Specifically, our results suggest that the cortical network is less tightly integrated than its spatial constraints would allow, but more strongly segregated than its spatial constraints would necessitate. We additionally find that hierarchical organisation and rich-club structure of the cortical connectivity are largely preserved in spatial and reduced surrogates and hence may be partially attributable to cortical wiring constraints. In contrast, the high modularity and strong s-core of the high-resolution cortical network are significantly stronger than in the surrogates, underlining their potential functional relevance in the brain

The added value of participatory modelling in fisheries management – what has been learnt?

How can uncertain fisheries science be linked with good governance processes, thereby increasing fisheries management legitimacy and effectiveness? Reducing the uncertainties around scientific models has long been perceived as the cure of the fisheries management problem. There is however increasing recognition that uncertainty in the numbers will remain. A lack of transparency with respect to these uncertainties can damage the credibility of science. The EU Commission's proposal for a reformed Common Fisheries Policy calls for more self-management for the fishing industry by increasing fishers' involvement in the planning and execution of policies and boosting the role of fishers' organisations. One way of higher transparency and improved participation is to include stakeholders in the modelling process itself. The JAKFISH project (Judgment And Knowledge in Fisheries Involving StakeHolders) invited fisheries stakeholders to participate in the process of framing the management problem, and to give input and evaluate the scientific models that are used to provide fisheries management advice. JAKFISH investigated various tools to assess and communicate uncertainty around fish stock assessments and fisheries management. Here, a synthesis is presented of the participatory work carried out in four European fishery case studies (Western Baltic herring, North Sea Nephrops, Central Baltic Herring and Mediterranean swordfish), focussing on the uncertainty tools used, the stakeholders' responses to these, and the lessons learnt. It is concluded that participatory modelling has the potential to facilitate and structure discussions between scientists and stakeholders about uncertainties and the quality of the knowledge base. It can also contribute to collective learning, increase legitimacy, and advance scientific understanding. However, when approaching real-life situations, modelling should not be seen as the priority objective. Rather, the crucial step in a science–stakeholder collaboration is the joint problem framing in an open, transparent way

Perceptual and conceptual processing of visual objects across the adult lifespan

Abstract: Making sense of the external world is vital for multiple domains of cognition, and so it is crucial that object recognition is maintained across the lifespan. We investigated age differences in perceptual and conceptual processing of visual objects in a population-derived sample of 85 healthy adults (24–87 years old) by relating measures of object processing to cognition across the lifespan. Magnetoencephalography (MEG) was recorded during a picture naming task to provide a direct measure of neural activity, that is not confounded by age-related vascular changes. Multiple linear regression was used to estimate neural responsivity for each individual, namely the capacity to represent visual or semantic information relating to the pictures. We find that the capacity to represent semantic information is linked to higher naming accuracy, a measure of task-specific performance. In mature adults, the capacity to represent semantic information also correlated with higher levels of fluid intelligence, reflecting domain-general performance. In contrast, the latency of visual processing did not relate to measures of cognition. These results indicate that neural responsivity measures relate to naming accuracy and fluid intelligence. We propose that maintaining neural responsivity in older age confers benefits in task-related and domain-general cognitive processes, supporting the brain maintenance view of healthy cognitive ageing

Distinct components of cardiovascular health are linked with age-related differences in cognitive abilities

Cardiovascular ageing contributes to cognitive impairment. However, the unique and synergistic contributions of multiple cardiovascular factors to cognitive function remain unclear because they are often condensed into a single composite score or examined in isolation. We hypothesized that vascular risk factors, electrocardiographic features and blood pressure indices reveal multiple latent vascular factors, with independent contributions to cognition. In a population-based deep-phenotyping study (n = 708, age 18–88), path analysis revealed three latent vascular factors dissociating the autonomic nervous system response from two components of blood pressure. These three factors made unique and additive contributions to the variability in crystallized and fluid intelligence. The discrepancy in fluid relative to crystallized intelligence, indicative of cognitive decline, was associated with a latent vascular factor predominantly expressing pulse pressure. This suggests that higher pulse pressure is associated with cognitive decline from expected performance. The effect was stronger in older adults. Controlling pulse pressure may help to preserve cognition, particularly in older adults. Our findings highlight the need to better understand the multifactorial nature of vascular aging

Poorer White Matter Microstructure Predicts Slower and More Variable Reaction Time Performance: Evidence for a Neural Noise Hypothesis in a Large Lifespan Cohort

Most prior research has focused on characterizing averages in cognition, brain characteristics, or behavior, and attempting to predict differences in these averages among individuals. However, this overwhelming focus on mean levels may leave us with an incomplete picture of what drives individual differences in behavioral phenotypes by ignoring the variability of behavior around an individual's mean. In particular, enhanced white matter (WM) structural microstructure has been hypothesized to support consistent behavioral performance by decreasing Gaussian noise in signal transfer. Conversely, lower indices of WM microstructure are associated with greater within-subject variance in the ability to deploy performance-related resources, especially in clinical populations. We tested a mechanistic account of the “neural noise” hypothesis in a large adult lifespan cohort (Cambridge Centre for Ageing and Neuroscience) with over 2500 adults (ages 18-102; 1508 female; 1173 male; 2681 behavioral sessions; 708 MRI scans) using WM fractional anisotropy to predict mean levels and variability in reaction time performance on a simple behavioral task using a dynamic structural equation model. By modeling robust and reliable individual differences in within-person variability, we found support for a neural noise hypothesis (Kail, 1997), with lower fractional anisotropy predicted individual differences in separable components of behavioral performance estimated using dynamic structural equation model, including slower mean responses and increased variability. These effects remained when including age, suggesting consistent effects of WM microstructure across the adult lifespan unique from concurrent effects of aging. Crucially, we show that variability can be reliably separated from mean performance using advanced modeling tools, enabling tests of distinct hypotheses for each component of performance

Ageing increases reliance on sensorimotor prediction through structural and functional differences in frontostriatal circuits

This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Nature Publishing Group.The control of voluntary movement changes markedly with age. A critical component of motor control is the integration of sensory information with predictions of the consequences of action, arising from internal models of movement. This leads to sensorimotor attenuation – a reduction in the perceived intensity of sensations from self-generated compared to external actions. Here we show that sensorimotor attenuation occurs in 98% of adults in a population-based cohort (n=325; 18-88 years; the Cambridge Centre for Ageing and Neuroscience). Importantly, attenuation increases with age, in proportion to reduced sensory sensitivity. This effect is associated with differences in the structure and functional connectivity of the pre-supplementary motor area (pre-SMA), assessed with magnetic resonance imaging. The results suggest that ageing alters the balance between the sensorium and predictive models, mediated by the pre-SMA and its connectivity in frontostriatal circuits. This shift may contribute to the motor and cognitive changes observed with age.Cam-CAN research was supported by the Biotechnology and Biological Sciences Research Council (BB/H008217/1). JBR and NW were supported by the James S. McDonnell Foundation 21st Century Science Initiative, Scholar Award in Understanding Human Cognition. JBR was also supported by Wellcome Trust [103838] and the Medical Research Council [MC-A060-5PQ30]. DMW was supported by the Wellcome Trust [097803], Human Frontier Science Program and the Royal Society Noreen Murray Professorship in Neurobiology. RNH was supported by the Medical Research Council [MC-A060-5PR10]. RAK was supported by a Sir Henry Wellcome Trust Postdoctoral Fellowship [107392]. LG was funded by a Rubicon grant from the Netherlands Organisation for Scientific Research (NWO)

Denial of long-term issues with agriculture on tropical peatlands will have devastating consequences

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